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Warning: this course contains shocking materials and is not recommended for viewing to persons with weak psyche, minors and pregnant women.
The course describes subject and methods of Pathophysiology, its place within system of biomedical sciences and history. It includes General Nosology (concept of health and disease, general etiology and pathogenesis, pathological processes and states, role of causal factors, conditions, reactivity and somatotype in pathology). It gives systematic of locally and centrally driven typical pathological processes: arterial, venous and combined hyperemiae, stasis, inflammation, immunopathological processes (including allergy and autoimmune disorders) acute phase response, fever, stress, shock, etc. Course deals with functional, metabolic and informational aspects of typical pathologic processes, like disorders of signaling, reception, post – receptor translation, programming and program archiving, conflicts of programs in living systems. It contains the consequent analysis of the injury and defensive responses as regards separate cells, organs and tissues and the whole organism. The lectures based on author’s original three-volumed textbook and workshop in Pathophysiology republished in Russia many times.

Taught By

Churilov Leonid Pavlovich

Associate Professor, Full Member of International Academy of Sciences (Health and Ecology)

Transcript

[MUSIC] Our previous talk was about normal conditions, how it is structured and regulated in health. Now about disease. There are three major typical pathological processes in microcirculation system. These are hyperaemia, ischaemia, and stasis. And all of them can occur separately, or as mosaic elements within a structure of bigger, more complicated pathological processes. For example, hyperaemia and stasis are embedded, as elements, into the structure of inflammation. Or for example, in thrombosis of arteriolae, a person is going to have ischaemia. In thrombosis of venulae, a person is going to have venous hyperaemia, and so on. So three major, typical pathological processes. Hyperaemia, local increase of blood supply and/or blood content in organ or in portion of tissue. Ischemia, local decrease of blood supply and blood content in organ or tissue portion. Stasis, local stop of blood flow in vessels, obligatory and within vessels. Here you can see the principle drawing of normal circulation, hyperaemia. Hyperaemia can be different. We distinguish between arterial, or active hyperaemia, with increase of blood velocity. And passive, or venous, hyperaemia, or venous congestion in English-speaking countries, which is hyperaemia with decrease of blood flow velocity. Now look at this picture and think of modelling, how to model these microcirculatory disorders. For a experimental model, we use a Cohnheim heritage, the transparent organs of a frog, like tongue, interdigital membrane of posterior leg, or intestinal mesentherium. And the main model is existing for almost a century and a half, and still valid. This is a person, a younger contemporary of Julius Cohnheim, who suggested how to interpret the results of this modelling. This is Vladimir Vasilievich Voronin, a Russian pathophysiologist, by the way, teacher of Nobel Prize winner Ivan Pavlov. And Voronin suggested by a physical frame for interpretation of microcirculatory disorder modelling. And the main result, Was the description of a phenomena you can see in this movie. The description of this phenomena in this kind of table, we call it Voronin's table. And in, first, left column, you can see various parameters which we need to take into consideration interpreting the microcirculatory disorders. First group of parameters most essential. It is related to inflow of blood and outflow of blood. As soon as you understand what happened to inflow and outflow, you can understand the whole dynamic of hyperaemia, or ischaemia, or venous congestion, or stasis. The next thing to evaluate is diameter of the major microvessels. What happens to arteriolae diameter, venulae diameter, capillaries, as regards to its diameter and its number per square millimeter of tissue? The next group of parameters is biophysical. It belongs to pressure characteristics. What happens to blood pressure in arteriolae, what happens to blood pressure in venulae? What is the difference in pressure between arteriolae and venulae, and how it changes in certain microcirculatory disorder? Also, we are interested in blood velocity, blood speed, what happens to volume speed of blood, what happens to linear speed of blood, and how blood flow looks. Is there some separation of blood layers visible in microscope? Or the blood flow is turbulent without delineation of plasma layer and blood cell layer. The next group of parameters characterizing the disorders of microcirculation belongs to chemistry. It is partial pressure of oxygen in tissue, how it changes during disorder. Also, oxygen difference between arteriolae and venulae. Also, a very important parameter is pH parameter, how the acidity of tissue changes when a certain microcirculatory disorder develops. And finally, we evaluate temperature, how it changes. Tissue fluid formation, is it changed or not? Lymph drainage, is it altered or not? Presence of oedema, if a certain disorder can produce oedema or cannot produce it. And maybe of great importance for practical medicine is a visual habitus of involved organ or tissue. Its color, its warmth or coldness, and different visible growth consequences of hyperaemia or ischaemia. Now we can compare all this set of parameters in three major Microcirculatory disorders in active hyperemia, in passive hyperemia, and in ischemia. And you can see that virtually all of them are different in these different disorders. Arterial inflow of blood is increased in active hyperemia, not changed in passive hyperemia, and decreased in ischemia. Arterial inflow, then we will look to the venous end of the system. What about venous outflow? And you can see in that in arterial hyperemia, venous outflow is equal to inflow, and it is also increased. But in venous condition or passive hyperemia, the situation is different. Venous outflow is always smaller than arterial inflow, so it is decreased compared to inflow. And in ischemia, inflow and outflow are both decreased and equal to each other. The same thing with all other parameters. For example, if you will look on the lumen of, Vessels, you can see that arterial hyperemia, active one is characterized by increase in our arteriole diameter, equal increase in venule diameter, and the total number of functioning capillaries is also increased. The situation is a little bit different in passive hyperemia, because arterial diameter in pure classic passive venous hyperemia is not changed. Absolutely different situation with venous diameter, because venules are distended by the increased amount of venules blood. And their diameter in passive hyperemia used to increase, sometimes greatly increased. What about capillaries? Total number of capillaries in venous hyperemia is not changed, but the venous portion of capillary is distended. And its diameter may be increased if you will look on similar set of parameters in ischemia. You can notice that the diameters of both arterial and venule are decreased in the total number, as well as lumen of capillaries is also decreased. I will not read aloud the whole table. Please, during self-studies, very attentively line by line, point by point, look it through and compare the main parameters in active hyperemia, passive hyperemia, and ischemia. And you will have complete knowledge about the comparative characteristics of three major microcirculatory disorders. Now, colleagues, Besides biophysical aspect, there is also pathophisiological aspect. And every disorder, I mean active active hyperemia, passive hyperemia, and ischemia has close consequences. The remote consequences, it has also some defensive value in certain situations, and some pathogenic potential for other situations. And you need to evaluate the remote and close sequels, defense or pathogenic roll of active hyperemia, passive hyperemia, ischaemia in every particular case. Speaking about consequences, please notice that active hyperemia proceeds with acceleration of blood flow with no congestion. That's why active hyperemia never produces edema. Passive hyperemia is another matter. The blood velocity is decreased, various congestion of blood outflow, Became smaller than arterial inflow. So any case of passive venous hyperemia will obligatory produce edema. Ischemia also is devoid of edema, because inflow and outflow are both small, decreased, but balanced. Speaking about remote consequences, active hyperemia has huge remote consequences for an organ or tissue. In chronic arterial hyperemia, there is always hypertrophy of involved organ, sometimes even hyperplasia. For example, chronic arterial hyperemia accompanies Grave's disease and thyrotoxic goiter in thyroid Gland, chronic arterial hyperemia accompanies hypertrophy of myocardium in. So active hyperemia may facilitate in chronic case hypertrophy, hyperplasia, acceleration of organogenesis and so on and so forth. Passive hyperemia is a different situation, chronic passive hyperemia can have rather deteriorating consequences, remote consequences for an organ or tissue. It can be hemorrhage per diapedesin fibrosis, excessive proliferation of stroma on account of decreased parenchymal proliferation. Step by step stromal elements can ooze out parenchymal ones in chronic, congested organs like in chronic venous congestion of lung. For example, you may get pneumosclerosis and brown induration of lung. Speaking about remote consequences of ischemia, we need to take into account that ischemia always means hypoxia. And even partial ischemia can facilitate organ atrophy in chronic case, and necrosis, and post-necrotic sclerosis. I want to emphasize that there are no bad and good processes. Every process is both bad and good in different proportions and in different situations. For example, arterial hyperaemia is very good for modelization of functional resources of involved organ or tissue. It can be used in thermal regulation, it can be involved in positive, necessary physiological reactions like tissue wash out or a physiological erection in nipples for example. But at the same time arterial hyperaemia is not always your friend, sometimes it is your foe. It may cause pathogenic consequences, for example in aneurysm. Like so-called berry aneurysms of blood vessels. Congenital ones, or formed in early ontogenesis. In aneurysms, active hyperaemia may cause aneurysm rupture and hemorrhage, which will result in headache, vertigo, and even more serious consequences, like stroke. Base of hyperaemia or venous congestion sometimes is interpreted negatively. But listen, it has obvious positive significance. For example, it contributes into barrier function of inflammation. It prevents the spread of germs, and inflammatory mediators beyond the borders of inflammatory focus. So it can be useful and defensive, it can be useful and defensive in inflammation, it promotes fibroplasia as a matter of regeneration process. It facilitates the thrombosis and the bleeding stops and so on, and so forth. But at the same time, passive hyperaemia of course can be pathogenic. For example, it can be responsible for circulatory hypoxia, and for organo sclerosis. Commonly, medical doctors always interpret ischaemia as negative phenomenon. And of course, it is responsible for circulatory hypoxia for necrosis of cells, for decrease of organ functional capacities, and so on and so forth. But at the same time, during bleeding, temporarily ischaemia of the damaged blood vessel is necessary for stop of bleeding. It takes part in hemostasis, it takes part in barrier function of inflammation, and it is necessary for redistribution of blood volume in organism between functioning and nonfunctioning organs. So every process can be either pathogenic or useful, it depends on situation. Now, speaking about main characteristics of this phenomena. Look at these pictures please, one picture depicts the diameter of the main micro circulatory vessels, and it changes during different micro circulatory pathological processes. And another picture, with columns, symbolize the dynamic of arterial inflow and venous outflow in every particular microcirculatory disorder. And you can see that in arterial hyperaemia, you have increase of both inflow and outflow and they are still equal to each other like in normal situations. There is no slowing of blood flow. There is no congestion in active arterial hyperaemia. Absolutely different situation in venous congestion. In venous congestion, inflow is always greater than outflow. There is a difference, that's why there is a congestion. Inflow is not changed compared to norm in pure classic venous hyperaemia, but outflow is always decreased. That is the main pathogenic mechanism of venous congestion. You can see also that there can exists combined or at mixed hyperaemia. And in these process, inflow is increased like in arterial hyperaemia, but outflow is decreased compared to inflow, like in the venous congestion. Combined hyperaemia is a matter of special talk later. As a rule, it is transient state between arterial hyperaemia and venous congestion. And finally, please look at the columns symbolizing the inflow and outflow in ischaemia. They both are decreased, but equal between each other. So in ischaemia, you have degrees of blood content, but without any edema. If you will look on the round pictures, you can appreciate what happens to the diameter of arteriola, venula, what happens to the number of functioning capillaries. And the diameter in every particular disorder of micro circulations. Well more complicated, but also important thing is to evaluate the dynamic of inflow and outflow pressure gradients, I mean oxygen pressure. You can see that oxygen pressure in arteriola is always higher than in venula, and it is even more so in arterial hyperaemia, but in ischemia or in venous congestion these difference diminishes.

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